Density analysis of organisms by magnetic levitation

Abstract

A device and methods for detecting the effect of compounds on an organism are provided. Furthermore, the device and methods disclosed herein allow for the fractionation of complex samples and the isolation of one or more organisms for the samples. The device and methods also allow for the study of development of the organism.

We claim: 
     
         1 . A method for detecting an effect of a compound of interest on a biological system, comprising:
 contacting a test sample comprising an organism with the compound of interest;   applying a magnetic field to the test sample in a paramagnetic solution;   determining the density of the organism in the test sample, wherein the organism occupies a position in the magnetic field that corresponds to its density;   comparing the density or location of the organism in the test sample to a reference density or location of an untreated reference organism; and   detecting the effect of the compound of interest on a biological condition based on a change in density of the organism.   
     
     
         2 . The method of  claim 1 , wherein location of the organism in the test sample is determined at different time points. 
     
     
         3 . The method of  claim 1 , wherein the change in density in the organism is an indication of altered fat content when the organism is in the presence of the compound of interest. 
     
     
         4 . The method of  claim 1 , wherein the change in density in the organism is indicative of uptake and accumulation of the compound of interest by the organism. 
     
     
         5 . The method of  claim 1 , further comprising:
 providing a plurality of test samples comprising the organism;   introducing a different compound of interest into each of the plurality of test samples; and   identifying those test samples containing organism contacted with the different compound of interest that demonstrate a change in density or location relative to the reference density or location of a reference organism that is not contacted with the different compound of interest, wherein the change in density or location is indicative of a biological effect on the organism.   
     
     
         6 . The method of  claim 1 , wherein the organism is an embryo, a bacterium, a protist, an ova, a spermatozoa, a nematode, a eukaryotic cell, or combinations thereof. 
     
     
         7 . The method of  claim 1 , wherein the organism is a plant tissue, a seed, a seedling, a tumor, a cancer mass, a group of cells, a spore, a pollen granule, a worm, or a multicellular parasite. 
     
     
         8 . The method of  claim 6 , wherein detecting the effect of the compound of interest is a change in embryonic development. 
     
     
         9 . The method of  claim 5 , further comprising separating the plurality of samples using a microfluidic device. 
     
     
         10 . A method for determining the toxicity of a compound on a biological system, comprising:
 contacting a plurality of test samples comprising an organism to a compound of interest at increasing concentrations;   applying a magnetic field to the test samples;   determining the density of the organism in the plurality of test samples, wherein the organism occupies a position in the magnetic field that corresponds to its density;   identifying the density in the test sample with a level of altered fat content of the organism, wherein a preselected level of fat content is associated with toxicity; and   determining a concentration of the compound of interest that provides a density in the organism associated with toxicity.   
     
     
         11 . A method of evaluating an embryo, comprising:
 exposing a paramagnetic solution comprising an embryo to a magnetic field, wherein the embryo occupies a position in the magnetic field that is an indication of its density;   monitoring the position of the embryo with time; and   detecting a change in location over time, the change in location being associated with gestational development of the embryo.   
     
     
         12 . The method of  claim 11 , wherein the change in density or position identifies a change in gestational growth rate. 
     
     
         13 . A method of sorting a population of organisms, comprising:
 exposing a paramagnetic solution comprising a population of organisms to a magnetic field, wherein individual members of the population occupy positions in the magnetic field that correspond to their densities; and   sorting the population based on its position in the magnetic field.   
     
     
         14 . The method of  claim 13 , further comprising isolating the population from the paramagnetic solution. 
     
     
         15 . A method of analyzing a sample for the presence of an organism, comprising:
 exposing a test sample to a magnetic field;   determining positions in the magnetic field of one or more constituent components of the test sample, wherein the positions are characteristic of their densities; and   detecting the presence or absence of a component at a predetermined position in the magnetic field that is associated with the presence or absence of the organism in the test sample.   
     
     
         16 . The method of  claim 15 , wherein the sample is a biological sample. 
     
     
         17 . The method of  claim 16 , wherein the biological sample is selected from the group consisting of bodily fluids and body tissues. 
     
     
         18 . The method of  claim 15 , wherein the organism has been preselected based on a characteristic of the organism. 
     
     
         19 . The method of  claim 18 , wherein the preselected organism is a parasite and the presence of the organism in the sample is indicative of parasitic infection. 
     
     
         20 . A method of analyzing an organism of interest, comprising:
 providing a paramagnetic solution of a composition and osmolality compatible with an organism of interest;   introducing the organism of interest into the paramagnetic solution;   applying a magnetic field to the paramagnetic solution; and   detecting density of the organism of interest by determining the position of the organism of interest in the magnetic field.   
     
     
         21 . The method of  claim 20 , wherein the paramagnetic solution comprises a chelated paramagnetic salt. 
     
     
         22 . The method of  claim 21 , wherein the chelated paramagnetic salt comprising manganese. 
     
     
         23 . The method of  claim 20 , wherein the paramagnetic solution further comprises a paralyzing agent. 
     
     
         24 . The method of  claim 20 , wherein the temperature of the paramagnetic solution is lower than the optimal temperature of the organism. 
     
     
         25 . The method of  claim 20 , wherein the organism is selected from the group consisting of prokaryotic cells, eukaryotic cells, parasitic worms, ova, embryos and spermatozoa. 
     
     
         26 . The method of  claim 20 , wherein the organism is a plant tissue, a seed, a seedling, a tumor, a cancer mass, a group of cells, a spore, a pollen granule, a worm, or a multicellular parasite. 
     
     
         27 . A device for determining the effect of a compound on a biological system, comprising:
 a pair of permanent magnets positioned to provide a magnetic field of a predetermined field gradient;   a sample holder located within the magnetic field for receiving a sample comprising an organism; and   a scale affixed to the magnet pair for use in determining the relative and/or absolute positions of organisms viewable in a sample.   
     
     
         28 . The device of  claim 27 , wherein the sample is configured to receive a sample comprising a suspension of organisms housed in a microfluidic chip. 
     
     
         29 . The method of  claim 1 , wherein the change in density in the organism is an indication of altered water content when the organism is in the presence of the compound of interest.